Complications associated with atherosclerotic vascular disease including heart attacks, stroke, and ischemic limbs are major medical problems. The implantation of intravascular stents, including drug-eluting stents and bare metal stents, to maintain the patency of blood vessels has become the standard of care for the treatment of a number of disorders including, for example, symptomatic coronary artery disease, cerebrovascular disease, and peripheral arterial disease.
Coronary stent implantation currently is a $6 billion business, with Americans receiving an estimated 1.5 million stents per year. One issue associated with the use of bare metal stents is the incidence of restenosis (scar tissue formation), which is the recurrence of narrowing of the blood vessel following stent implantation. A variety of drug-eluting stents have been developed to address this issue, and polymer-based sirolimus-eluting stents (Cypher, Cordis Corp., Miami Lakes, Fla.) and paclitaxel-eluting stents (Taxus, Boston Scientific Corp., Natick, Mass.) and zotarolimus-eluting stents (Endeavor, Medtronic) and everolimus-eluting stents (Xience, Abbott Vascular) have been approved for human use in the United States of America. Since their introduction several years ago, drug-eluting stents have captured approximately 70-80% percent of the U.S. stent market, due mainly to their ability to prevent or reduce the incidence of restenosis.
Recently, the enthusiasm of drug eluting stents has been dampened by safety concerns associated with an increased risk of stent thrombosis occurring more than 30 days after implantation (termed late stent thrombosis). It appears that late stent thrombosis occurs more frequently following implantation of drug eluting stents relative to bare metal stents. (See, Nakazawa et al. (2007) AM. J. CARDIOL. 100: 36M-44M; Joner et al. (2006) J. AM. COLL. CARDIO. 48:193-202.) The emergence of late stent thrombosis, i.e., thrombosis occurring more than 30 days after implantation, resulting from the use of drug-eluting stents is causing medical, legal, and financial concerns for clinicians, patients, stent companies, and regulatory authorities. The problem of stent thrombosis is likely to persist indefinitely with the current generation of drug eluting stents, as stent thrombosis occurs steadily at a rate of 0.4-0.6% per year (Wenaweser et al. (2008) J. AM. COLL. CARDIO. 52:1134-1140).
Due to the association between late stent thrombosis and high morbidity rates, there exists a need for approaches that permit the identification of subjects at risk of developing stent thrombosis well before the onset of clinically-apparent symptoms, which, once identified, may be too late to treat the subject due to a high rates of myocardial infarction and death (Iakovou (2005) JAMA 293:2126-2130). Once subjects at risk of developing stent thrombosis have been identified they can be monitored more regularly and/or provided with or maintained on preventative or prolonged therapies, for example, anti-platelet or anti-coagulant therapies, so as to reduce the risk of stent thrombosis. Furthermore, there is an ongoing need to be able to evaluate the effectiveness of new anti-stent thrombosis therapies and therapeutic approaches (including but not limited to new stents, balloon catheters, drugs, or cells/biological therapies) in vivo in preclinical animal models, during clinical trials and in patients.